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P Astoul

Publications and source records attributed to P Astoul.

At least 19 recordsLinked to original sources

[Thymoma and disseminated lupus erythematosus. Two new cases and review of the literature].

INTRODUCTION: Thymoma is a tumour originating in the epithelial cells of the thymus, associated with several immunologic disorders. The association of thymoma with systemic lupus erythematosus has rarely been described. We report two cases of this association. EXEGESIS: Description of two cases and a review of the literature. Mr T. was 41 years old when the diagnosis of thymoma and lupus was made. The thymectomy did not influence the evolution of his lupus. Mrs G. had been treated because of a lupus for 8 years prior to developing a thymoma. One year later she presented with erythroblastopenia, which was only sensitive to cyclosporin. CONCLUSION: The association between lupus and thymoma has been reported in 36 cases in the literature. Thymoma is benign in 59% of the cases. The clinical presentation of lupus is nonspecific except for age, median 48 years, and sex ratio, 4:3. The clinical outcome of the lupus is not influenced by the thymectomy. Thymoma may precede lupus with a delay of several years or it may be diagnosed concurrently or several years later. This association is not accidental, though the pathogenic link between these conditions remains unknown. One could suppose that the decrease of the thymic function in the course of thymoma could enhance the expression of autoreactive T lymphocytes as well as the activation of B cells. Patients should be followed after thymectomy because autoimmune diseases, particularly lupus, may develop belatedly. On the other hand, thymoma may be suspected mainly when lupus occurs in patients around 50 years of age.

Adult↗

[Standards, options and recommendations for the management of locally advanced non small cell lung carcinoma].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the management of locally advanced non small cell lung carcinoma. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations are: 1) The management of the locally advanced non small cell lung carcinoma has two main goals: firstly to obtain local control of the disease (or to at least delay local progression in order to improve the survival or relapse free survival), and secondly to prevent the development of metastases. 2) There is a consensus that locally advanced non small cell lung carcinoma should be irradiated. External beam radiotherapy should be of optimal quality and delivered at a minimal dose of 60 Gy by standard fractionation. For patients with a poor life expectancy, this can be delivered as a split-course or hypofractionated scheme. 3) Treatment for patients with a performance status of 0-1 should consist of short duration induction chemotherapy (with a least two drugs one of which must be cisplatin), combined sequentially with conventional radiotherapy. 4) Surgery is contraindicated in extensive N3 disease. Combined radio-chemotherapy (adjuvant or neoadjuvant) is not indicated outside clinical trials. Surgery is justified in stage N2 disease as good local control can be achieved. T4-N0 disease should be treated surgically with curative intent.

Adult↗

[Standards, Options and Recommendations for the management of stage I or II primary bronchial cancers treated exclusively with radiotherapy].

CONTEXT: The 'Standards, Options and Recommendations' (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French cancer centres and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the management of stage I and II non small cell lung carcinoma treated by radiotherapy alone. METHODS: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French cancer centres. RESULTS: The main recommendations for the management of stage I and II non small cell lung carcinoma treated by radiotherapy alone are: 1) The curative external irradiation with a continual course is an alternative to surgery only in the case of medically inoperable tumors or because the patient refuses surgery; 2) The external irradiation of the primary tumor only without the mediastinum could be proposed in peripheral stage IA. In proximal stage IA and IB, external irradiation should be carried out only as part of prospective randomised controlled trials comparing a localised irradiation of the primary tumor with a large irradiation of the mediastinum and the primary tumor. The treated volume must include the macroscopic tumoral volume with or without the microscopic tumoral volume and with a security margin from 1.5 to 2 cm; 3) There is a benefit to delivering a total dose in the primary tumor higher than 60 Gy in so far as the proposed irradiation, taking into account the respiratory function, does not increase the likelihood of severe adverse events due to radiation; and 4) The change in fractionation, the radiochemotherapy combination, the endobronchial brachytherapy with high dose rate alone or with external irradiation could be proposed only as part of prospective controlled trials for tumors classified as stage IB or II.

Aged↗

Alternating chemotherapy and accelerated split-course irradiation in locally advanced nonsmall cell lung carcinoma.

BACKGROUND: The prognosis of patients with locally advanced nonsmall cell lung carcinoma (NSCLC), which is usually unresectable, is very poor, and patient survival rarely reaches 1 year. However, prolonged survival correlated with objective responses has been observed among patients with intrathoracic disease treated with a combination of cytotoxic drugs and local irradiation despite the lack of consensus regarding the schedule of such combined therapy. From October 1989 to November 1993, a Phase II study was conducted to evaluate the tolerability and efficacy of alternating chemotherapy and accelerated split-course radiotherapy in the treatment of patients with locally advanced NSCLC. METHODS: Sixty-three consecutive patients with unresectable Stage III NSCLC entered this study. The treatment was composed of 3 cycles of combined chemotherapy and radiotherapy at 4-week intervals. Chemotherapy with cisplatin (30 mg/m2/day) and etoposide (100 mg/m2/day) was delivered intravenously on Days 1, 2, and 3, followed by radiotherapy on Days 4-8. A course of radiotherapy consisted of 1.5 gray (Gy) per fraction twice a day (3 Gy per day) for 5 consecutive days, for a total dose of 15 Gy. Response was assessed after 3 courses, for a total irradiation dose of 45 Gy. In cases of objective antitumoral response with operable tumor, surgery was performed. A fourth course of chemotherapy and radiotherapy, for a total dose up to 60 Gy in 12 weeks, was administered to all patients. Two additional courses of chemotherapy were given, for a total of six. RESULTS: Of the 63 patients, 62 were evaluable for response. Six had a complete remission and 36 a partial response, resulting in an overall response rate of 67.7%. Nine patients underwent surgery (pneumonectomy for seven patients and lobectomy for two patients), and the complete disappearance of any residual tumor was documented histologically in four. Of the 290 chemotherapy courses delivered, there were 31 of Grade 3-4 toxicity, mainly leukopenia and vomiting. The median times of freedom from disease progression and overall survival were 8 months (confidence interval [CI], 7-9.5) and 14 months (CI, 10-22), respectively. The 1-, 2-, and 5-year survival rates of the 62 patients were 54%, 35%, and 21%, respectively. Patients who responded had a significantly longer median survival (16 months) than nonresponders (7 months) (P = 0.02). However, there was no difference in the survival of resected and nonresected patients. CONCLUSIONS: This treatment schedule resulted in a high response rate with prolonged survival. However, the toxicity of this approach was not negligible, even though it did not preclude this strategy. This combined modality must be compared with other combinations of alternating or sequential chemoradiotherapy.

Aged↗

Results of a phase II trial of combined chemotherapy for patients with diffuse malignant mesothelioma of the pleura.

BACKGROUND: Malignant pleural mesothelioma is associated with a poor prognosis because of its resistance to treatment. The authors conducted a Phase II trial in which two drugs (etoposide and 5-fluorouracil) were added to the Cancer and Leukemia Group B cisplatin-mitomycin regimen in an effort to define a more effective chemotherapy. METHODS: Forty-five patients with confirmed Stage II malignant pleural mesothelioma were prospectively enrolled in the study. Thirty-one patients received cisplatin 60 mg/m2 on Day 1, 5-fluorouracil 600 mg on Days 1-4, folinic acid 100 mg/m2 on Days 1-4, mitomycin C 10 mg/m2 on Day 3, and etoposide 100 mg/m2 i.v. on Days 1-3, with prophylactic hematopoietic growth factors. Fourteen patients received cisplatin, 5-fluorouracil, folinic acid, and mitomycin C with the protocol unchanged, and oral etoposide 50 mg on Days 1-21 without growth factors (1 cycle every 28 days). Histology included epithelial (in 33 cases), sarcomatous (in 6), mixed (in 3), and unspecified type (in 3). RESULTS: Two hundred eleven cycles were administered. Treatment was well tolerated and the major toxicity was hematologic: anemia in 30% of cases, neutropenia in 24%, and 2 probable cases of mitomycin-induced pneumonitis. The objective response rate was 38% (17 of 45 were partial responses), and the median response duration was 12 months. The median survival time was 16 months. There were no differences in response or survival between the 31 patients treated with growth factors and the 14 patients treated without them. Survival was slightly better for responders than for nonresponders who had stable disease or progression (20 vs. 10 months, P < 0.05). CONCLUSIONS: This four-drug combination was effective, with a notably high response rate, acceptable toxicity, and good adherence to protocol doses. The impact on survival was limited.

Adult↗

Pleural mesothelioma.

The increasing incidence of malignant pleural mesothelioma (MPM), better knowledge of its pathogenesis with a strong implication of asbestos fibers, and some promising therapeutic results have led to a new interest in the management of patients with this disease. The diagnosis of MPM is easier because of new immunohistochemical markers that recognize the mesothelial cells with good specificity and sensitivity on pleural biopsy samples ideally obtained by thoracoscopy. Moreover, this endoscopic procedure allows the physician to make the diagnosis of MPM at an early stage, which is the key of the therapeutic management of this disease. If radiotherapy is necessary in preventing the malignant seeding after pleural procedures in patients, the lack of comparative studies did not show the superiority of a given treatment against another. A new international staging of the disease, however, allows physicians to discriminate several groups of patients for such comparative studies--in particular, for testing the efficacy of intrapleural therapy, e.g., cytokines--for early-stage MPM and multimodal management, i.e., extrapleural pneumonectomy, radiotherapy, and chemotherapy for more advanced diseases, has led to prolonged survival in carefully selected patients. To reach this target, all patients must be enrolled in protocols. The usual pessimism for the management of patients with malignant pleural mesothelioma is over.

Combined Modality Therapy↗

[Mucoepidermoid bronchial tumor with an unusual radiologic presentation].

We report a case of low-grade malignant mucoepidermoid bronchial tumor in a 21-year-old woman who presented with hemoptysis. There was a striking radiological presentation with a unilateral clear radiograph. Lung scintigraphy demonstrated perturbed ventilation and perfusion of the left lung. Pulmonary angiography only showed diminished peripheral vascularization. The main vessels were clear. These anomalies fit the radiological category of air trapping accompanied by probably hypoxic pulmonary vasoconstriction. Mucoepidermoid tumors account for only 0.5-1% of all primary lung tumors. They are found in adults as well as in children. There are two clear-cut histological forms with very different prognosis. The tumors of high-grade malignancy are considered as undifferentiated carcinomas and should be treated as such. The prognosis is much better for tumors of low-grade malignancy and current treatment is surgical in the absence of recurrence after isolated endoscopic treatment.

Adult↗

[Disseminated histoplasmosis caused by Histoplasma capsulatum with cerebral involvement occurring 13 years after the primary infection].

A 49-year-old man with disseminated histoplasmosis (pulmonary and central nervous system involvement) successfully treated with ketoconazole and fluconazole combination is reported. Histoplasma capsulatum infection of the central nervous system is extremely rare in France partly because the organism is not endemic. Oral treatment with newer triazoles may be useful for central nervous system histoplasmosis, but additional information is needed to establish their effectiveness.

Antifungal Agents↗

[Endoscopic diagnosis of mesothelioma].

Mesothelioma is a rare disease but its incidence is rising. Diagnosis is still difficult but has been improved by immunohistochemical techniques and panels of pathologists. At the present time thoracoscopy is the most sensitive method for diagnosis of mesothelioma and a good alternative to thoracotomy. The main indication for thoracoscopy is unexplained pleurisy that cannot be diagnosed by needle biopsy. Thoracoscopy allows diagnosis in 95% of cases. Pleural ultrasound can be useful for diagnosis of limited pleurisy without multiple radiation exposure. Thoracoscopy is usually performed under light general anesthesia using a rigid endoscopic system. If possible, pneumothorax should be induced the day before the procedure to allow better assessment of the entry route and prevent adherences or symphysis. Tolerance of thoracoscopy is excellent. Thoracoscopy allows not only complete visualization of the pleural cavity including the diaphragmatic visceral pleura and the lung but also multiple biopsies. In early stage disease, thoracoscopy permits distinction of patients with stage Ia (involvement confined either the parietal or diaphragmatic pleura and purely inflammatory aspect in 50% of cases) from patients with stage Ib (involvement of the visceral pleura). Median survival is 28.3 months for stage Ia versus 10 months for stage Ib. Endoscopic observation enables accurate staging of tumor involvement which is an important prognostic finding and is an essential technique for early diagnosis of mesothelioma.

Humans↗

[Malignant mesothelioma: clinical and therapeutic study].

Like lung cancer, mesothelioma is difficult to diagnose early. Nevertheless disease stage is the determinant factor for outcome of treatment. Effective diagnostic examinations must be undertaken promptly. Thoracoscopy is one of the best diagnostic procedures provided that it is skillfully performed to prevent complications such as development of subcutaneous nodules along the pathway of the trocar. Several arguments have been proposed against routine screening including low incidence of the disease, poor sensitivity and specificity of screening techniques, and lack of effective therapy documented by phase III study. However there are a number of arguments in favor of screening. The high-risk population is well defined. Although no control study is currently available, promising new results have been observed in limited forms, i.e., 62% response rate at stage IA with 39% survival at 5 years in patients presenting epithelial forms without lymph node involvement treated by pleuro-pneumonectomy, chemotherapy, and radiotherapy. Screening is necessary to recruit more early-stage patients for further clinical trials to improve therapeutic techniques. Poor outcome of treatment could be due to delayed diagnosis. Early diagnosis is also needed to allow compensation of occupational disease to begin while the patient is still alive.

Adult↗

Intrapleural administration of interleukin-2 for the treatment of patients with malignant pleural mesothelioma: a Phase II study.

BACKGROUND: The prognosis associated with malignant pleural mesothelioma (MPM) is poor in spite of surgery, radiotherapy, photodynamic therapy, or chemotherapy. Therefore, new therapeutic strategies, including intrapleural immunotherapy, are being investigated. Several clinical studies have demonstrated objective antitumoral responses to intrapleural interleukin-2 (IL-2) administration in the treatment of malignant pleurisy. The maximum tolerated dose, 24 x 10(6) IU/m2/day for 5 days, was determined in a Phase I study. Based on these results, a Phase II study was conducted, in which intrapleural IL-2 (21 x 10(6) IU/m2/day for 5 days) was given to patients with MPM. METHODS: Patients with histologically documented MPM were evaluated for response 36 days after treatment by computed tomography scan and thoracoscopy with biopsies. Toxicity was recorded and graded according to World Health Organization criteria. Survival was calculated from the start of treatment to death according to the Kaplan-Meier method, and the survival of responders and nonresponders was compared using the log rank test. RESULTS: Twenty-two patients entered this study. Of the 22 cases of MPM, 19 were epithelial, 2 were mixed, and 1 was fibrosarcomatous. Three patients had Stage IA disease, 1 had Stage IB, 16 had Stage II, 1 had Stage III, and 1 had Stage IV (Butchart classification). All patients received their planned treatment. No dose reduction or interruption occurred. There were 11 partial responses and 1 complete response. Stable disease occurred in 3 patients and disease progression in 7 patients. The overall median survival time was 18 months; the median survival time of responders differed significantly from that of nonresponders (28 months vs. 8 months, P < 0.01). The 24- and 36-month survival rates for responders were 58% and 41%, respectively. CONCLUSIONS: These results confirm that intrapleural administration of IL-2 is well tolerated and has antitumor activity in patients with MPM. The authors recommend a dose of 21 x 10(6) IU/m2/day for 5 days. However, determination of the schedule of IL-2 and its superiority to conventional treatment in a Phase III study has yet to be accomplished.

Adult↗

Diagnostic thoracoscopy.

Thoracoscopy provides diagnosis of pleural diseases with a high degree of accuracy. Moreover, this procedure allows a careful pleural staging of the disease, in particular for pleural cancer, which is important for the prognosis and therapeutic decision. This article focuses on the technique, indications, and results of medical thoracoscopy.

Biopsy↗

Cisplatin, ifosfamide, and vinorelbine combination chemotherapy in stage III-IV non-small-cell lung cancer: a phase II study.

The authors evaluate the combination of three drugs, vinorelbine, ifosfamide, and cisplatin, which have been shown to produce good response rates and a significant gain in survival when any two of them are given together. Seventy-seven untreated patients with inoperable stage III-IV non-small-cell lung cancer from three centers were included. The combination consisted of cisplatin 30 mg/m2 daily, ifosfamide 1,500 mg/m2 daily, mesna 1,500 mg/m2 daily on days 1-3, and vinorelbine 25 mg/m2 daily on days 1 and 8. Four cycles were administered every 4 weeks for a total of 267 cycles, before an assessment for toxicity, effective dose intensity, response rate, and survival was made. Toxicity was mainly hematologic (grade 3-4 neutropenia (15.7%), anemia (8.2%), and thrombopenia (2.6%)) but did not require granulocyte colony-stimulating factors. Objective response rate was 41.1% (95% confidence interval, 29.5-52.9%) in 68 patients suitable for assessment. The mean time to progression and median survival were 7.7 +/- 1.3 months and 11.6 months, respectively. One-year survival was 47.1%. The effective dose intensity of cisplatin and ifosfamide correlated strongly with survival, whereas stage and performance status did not. This study confirms previously reported favorable results for response and survival rates obtained in stage III-IV non-small-cell lung cancer with the vinorelbine, ifosfamide, and cisplatin combination. Respect of a scheduled dose intensity has a clear-cut influence on survival and should be evaluated routinely in future polychemotherapy trials.

Adult↗

Malignant pleural mesothelioma.

The incidence of malignant pleural mesothelioma (MPM) has risen for some decades and is expected to peak between 2010 and 2020. Up to now, no single treatment has been proven to be effective and death usually occurs within about 12-17 months after diagnosis. Perhaps because of this poor prognosis, early screening has incited little interest. However, certain forms may have a better prognosis when diagnosed early and treated by multimodal therapy or intrapleural immunotherapy. Diagnosis depends foremost on histological analysis of samples obtained by thoracoscopy. This procedure allows the best staging of the pleural cavity with an attempt to detect visceral pleural involvement, which is one of the most important prognostic factors. Although radiotherapy seems necessary and is efficient in preventing the malignant seeding after diagnostic procedures in patients, there has been no randomized phase III study showing the superiority of any treatment compared with another. However, for the early-stage disease (stage I) a logical therapeutic approach seems to be neoadjuvant intrapleural treatment using cytokines. For more advanced disease (stages II and III) resectability should be discussed with the thoracic surgeons and a multimodal treatment combining surgery, radiotherapy and chemotherapy should be proposed for a randomized controlled study. Palliative treatment is indicated for stage IV. In any case, each patient should be enrolled in a clinical trial.

Asbestos↗